The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide

Sophie Viaud (1, 2) , Fabiana Saccheri (2) , Gregoire Mignot (3) , Takahiro Yamazaki (2) , Romain Daillere (1, 2) , Dalil Hannani (2) , David P. Enot (4) , Christina Pfirschke (5) , Camilla Engblom (5) , Mikael J. Pittet (5) , Andreas Schlitzer (6) , Florent Ginhoux (6) , Lionel Apetoh (3) , Elisabeth Chachaty (7) , Paul-Louis Woerther (7) , Gerard Eberl (8) , Marion Berard (9) , Chantal Ecobichon (10, 11) , Dominique Clermont (12) , Chantal Bizet (12) , Valerie Gaboriau-Routhiau (13, 14) , Nadine Cerf-Bensussan (13, 14) , Paule Opolon (15) , Nadia Yessaad (16) , Eric Vivier (16) , Bernhard Ryffel (17) , Charles O. Elson (18) , Joel Dore (13) , Guido Kroemer (19, 20, 4, 21) , Patricia Lepage (13) , Ivo Gomperts Boneca (10, 11) , Francois Ghiringhelli (3, 22) , Laurence Zitvogel (1, 23, 2)

1 UP11 - Université Paris-Sud - Paris 11
2 UMR 1015 - Immunologie des tumeurs et immunothérapie
3 LNC - Lipides - Nutrition - Cancer (U866)
4 U848 - Apoptose, cancer et immunité
5 HMS - Harvard Medical School [Boston]
6 SIgN - Singapore Immunology Network
7 Microbiologie
8 Développement des Tissus Lymphoïdes
9 Animalerie centrale (Plate-forme)
10 Groupe Avenir
11 BGPB - Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall
12 CIP - Collection de l'Institut Pasteur
13 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
14 U989
15 IFR54 IRCIV, Institut de recherche intégrée en cancérologie, Laboratoire de Pathologie Expérimentale
16 CIML - Centre d'Immunologie de Marseille - Luminy
17 INEM - Immunologie et Neurogénétique Expérimentales et Moléculaires
18 UAB - University of Alabama at Birmingham [ Birmingham]
19 Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138 - Apoptose, cancer et immunité
20 Assistance Publique - Hôpitaux de Paris
21 UPD5 - Université Paris Descartes - Paris 5
22 Groupe Avenir [Dijon]
23 CIC 1428 , CBT 507 - Centre d'Investigation Clinique en Biotherapie des cancers

Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate antitumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of "pathogenic" T helper 17 (pT(H)17) cells and memory T(H)1 immune responses. Tumor-bearing mice that were germ-free or that had been treated with antibiotics to kill Gram-positive bacteria showed a reduction in pT(H)17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pT(H)17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.

Domaines: Sciences du Vivant [q-bio]

Sophie Viaud, Fabiana Saccheri, Gregoire Mignot, Takahiro Yamazaki, Romain Daillere, et al.. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science, 2013, 342 (6161), pp.971-976. ⟨10.1126/science.1240537⟩. ⟨hal-01204279⟩